HTLV-1 Virus

Human T-cell Lymphotropic Virus Type 1 (HTLV-1) is an RNA virus which belongs to the genus Deltaretrovirus, subfamily Orthoretrovirinae, family Retroviridae. In the latest International Taxonomy Committee of Viruses (ICTV) classification (8th report), this genus includes three primate species: Primate T-lymphotropic virus type 1, 2, and 3 (PTLV-1, PTLV-2, PTLV-3). Each PTLV species includes both human and simian (monkey and ape) viruses which are classified as isolates or strains, HTLV-1, HTLV-2, HTLV-3, and STLV-1, STLV-2, STLV-3 respectively. Deltaretrovirus also includes bovine leukemia virus that infects cattle.² All HTLV-1 subtypes described so far have most probably originated from separate interspecies transmissions from simians to humans.⁵

NCBI classification of Human T-lymphotropic virus 1:

• HTLV-1 subtype A
  • Human T-cell lymphotropic virus type 1 (Caribbean isolate)
  • Human T-cell lymphotropic virus type 1 (isolate MT-2)
  • Human T-cell lymphotropic virus type 1 (strain ATK)
  • Human T-cell lymphotropic virus type 1 (north American isolate)
• HTLV-1 subtype B
  • Human T-cell lymphotropic virus type 1 (African isolate)
• HTLV-1 subtype C
  • HTLV-1 isolate Mel 15

Retroviruses, such as HTLV-1 and human immunodeficiency virus differ from other RNA viruses in that they synthesize messenger RNA (mRNA) and replicate their genome by means of DNA components which they use to produce a double-stranded DNA called proviral DNA or provirus. Proviral DNA can then direct the production of new RNA virus genome copies. After proviral DNA has been manufactured, it is converted to a circular form and incorporated into the host cell chromosome. Sometimes these integrated viruses can change host cells into tumor cells.⁶

Locating the proviral DNA is the objective of the DNA viral load test using the polymerase chain reaction (PCR). The PCR acts as a molecular copy machine. It takes a strand of a nucleic acid (such as RNA or DNA) and multiplies it billions of times so that enough is available for detecting purposes.⁷ The RNA associated with HTLV-1 and HIV viruses is found in the blood plasma (blood minus blood cells) within circulating virus particles. The amount of this viral RNA concentration can be measured to determine the RNA viral load. The test is performed the same way as the DNA viral load test, except that RNA is copied and determined.

Malignant, Neurologic, and Inflammatory Diseases Linked To HTLV-1

HTLV-1 employs several means for inducing tumors. The viral oncoprotein called Tax plays a major role in the process of initiation and development of cancer. It binds to host cell proteins and inhibits the transcription of genes which regulate cell proliferation, programmed cell death (apoptosis), and DNA repair. By inactivating these important mechanisms, Tax protein stimulates the infected T-cells to proliferate uncontrollably which results in cancer.

Human T-cell Lymphotropic Virus Type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a cancerous growth of HTLV-1-infected T-cells with severe organ infiltration. HTLV-1 also causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a nonmalignant demyelinating neurologic disorder. The viral load of HTLV-1 is higher in patients with HAM/TSP than in HTLV-1 infected patients who do not have clinical signs.⁸ HTLV-1 has also shown to be associated with several inflammatory diseases, such as alveolitis, polymyositis, arthritis, uveitis, and Sjorgen's syndrome.⁴ HTLV-1 occurs worldwide. An estimated 10-20 million people are currently infected with HTLV-1. In 1996, the virus has been classified as carcinogen. HTLV-1 is endemic in the Caribbean area, Japan, and some areas of Africa. Infections with this virus have also been documented in the United States.

Transmission routes include breastfeeding, sexual contact, infected blood, and sharing of needles among intravenous drug users. Saliva has also been suggested as a route of transmission.² Most infected individuals develop ATLL 20-30 years after the exposure to the virus and do not have symptoms throughout their life. The early stage of ATLL is characterized by general malaise, fever, abnormal lymph nodes, enlarged liver, jaundice, drowsiness, weight loss, and infections. Skin rash, papules, nodules and bone lesions are commonly seen. As the disease progresses, affected individuals may experience extreme weakness, back pain, and incontinence.^1,2

ATLL is a highly aggressive malignancy and patients usually die within 1-2 years of diagnosis, typically due to infections, excess of calcium in the blood (hypercalcemia) and bone lesions. Infections are most often caused by Pneumocystis carinii, Aspergillus fumigatus, Cryptococcus neoformans, Strongyloides stercoralis, Mycobacteria tuberculosis, and cytomegalovirus.³

The serious risk of HTLV-1 infection among susceptible groups in the United States, Japan, and Europe has led to public health intervention policies such as blood donor screening to prevent contaminated blood from entering the blood supply. The presence of HTLV-1 antibodies in a donor excludes that person from donating blood.¹

Prevention of infection with HTLV-1 may be accomplished by several methods. First, screening pregnant women and discouraging those who are infected with HTLV-1 from breastfeeding can substantially reduce occurrence of ATLL. Second, screening blood donations which has been shown to be highly effective in reducing HTLV-1 transmission.

Related Topics